Luteolin inhibits ER-α expression through ILK inhibition is regulated by a pathway involving Twist and YB-1. (March 2018)

• Record Type: Journal Article
• Authors: Lin, Ying-Chao; Liu, Liang-Chih; Ho, Chi-Tang; Hung, Chao-Ming; Way, Tzong-Der
• Is Part Of: Journal of functional foods. Volume 42(2018)
• Page Start: 75
• Page End: 84
• Publication Date: 2018-03
• Subjects: Luteolin -- ER-α -- YB-1 -- ILK -- EMT; DMEM/F12 Dulbecco's Modified Eagle's Medium/Nutrient Mixture F12 -- DMSO dimethyl sulfoxide -- ECL enhanced chemiluminescence -- EMT epithelial-mesenchymal transition -- ER-α estrogen receptor alpha -- FBS fetal bovine serum -- ILK Integrin-linked kinase -- MTT 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide -- RPMI 1640 Roswell Park Memorial Institute (RPMI) 1640 -- SDS-PAGE sodium dodecyl sulfatepolyacrylamide -- YB-1 Y-box binding protein-1; Functional foods -- Analysis -- Periodicals; Food -- Biotechnology -- Periodicals; Nutrition -- Periodicals; 613.2
• DOI: 10.1016/j.jff.2017.12.059
• Languages: English
• ISSNs: 1756-4646

Abstract

Highlights: Luteolin inhibited the expression of ER-α through the downregulation of YB-1. Luteolin downregulated Twist expression. Luteolin downregulated Hif-1α expression. Luteolin suppressed YB-1 expression through the downregulation of ILK/Akt/STAT3-regulated Twist expression. Luteolin inhibited epithelial-mesenchymal transition. Abstract: Increasing evidence supports the anti-estrogenic and/or anti-proliferative properties of luteolin, which is a natural flavonoid existing in herbs, vegetables and fruits. However, the molecular mechanisms responsible for these effects are only partially explored. In the present study, estrogen receptor-alpha (ER-α) was identified as a potential molecular target for luteolin. Our data indicated that treatment with luteolin engendered suppression of ER-α protein and mRNA expression in ER-α-positive breast cancer cells. Y-box binding protein-1 (YB-1) is a known transcriptional regulator of ER-α expression. In this studies it was demonstrated that luteolin decreased YB-1 protein and mRNA expression. Integrin-linked kinase (ILK) is able to phosphorylate many downstream effectors that have the potential to regulate YB-1 transcription. We provided evidence for a mechanism by which luteolin suppressed YB-1 expression through the downregulation of ILK/Akt/STAT3-regulated Twist expression in ER-α-positive breast cancer cells. Our data also showed that luteolin inhibited cancer migration and invasion through the inhibition of epithelial-mesenchymal transition (EMT). Taken together, these data indicate that the antitumorigenic effects of luteolin in ER-α-positive breast cancer cells may arise from its ability to reduce ER-α expression.